CN103147225A - Preparation method for protein-polyose-polylactic acid polycaprolactone vascular stent - Google Patents
Preparation method for protein-polyose-polylactic acid polycaprolactone vascular stent Download PDFInfo
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- CN103147225A CN103147225A CN2013100479469A CN201310047946A CN103147225A CN 103147225 A CN103147225 A CN 103147225A CN 2013100479469 A CN2013100479469 A CN 2013100479469A CN 201310047946 A CN201310047946 A CN 201310047946A CN 103147225 A CN103147225 A CN 103147225A
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Abstract
The invention relates to a preparation method for a protein-polyose-polylactic acid polycaprolactone vascular stent. The method comprises the following steps: (1) completely dissolving chitosan into a hexafluoroisopropanol and trifluoroacetic acid mixed solution to obtain a chitosan solution; (2) completely dissolving collagen into hexafluoroisopropanol to obtain a collagen solution; (3) completely dissolving polylactic acid polycaprolactone into hexafluoroisopropanol to obtain a polylactic acid polycaprolactone solution; and (4) mixing and stirring the chitosan solution, the collagen solution and the polylactic acid polycaprolactone solution to obtain a protein-polyose-polylactic acid polycaprolactone spinning solution, and then achieving static spinning to obtain the protein-polyose-polylactic acid polycaprolactone vascular stent. The prepparation materials have superior biocompatibility and mechanical property; and the designed multi-component composite biological material has a broad application prospect, and the preparation method is simple and feasible and is mainly used in small-caliber vascular tissue engineering.
Description
Technical field
The invention belongs to the preparation field of scaffold for vascular tissue engineering, particularly the preparation method of a kind of albumen-polysaccharide-polylactic acid poly caprolactone intravascular stent.
Background technology
Day by day serious along with the disease such as tissue defect and organ failure clinically, the common prosthetic even organ transplant needs, the especially angiocardiopathy that have been difficult to satisfy sufferer becomes one of grave danger of human health (Canver CC.Conduit Options in Coronary Artery Bypass Surgery.CHEST Journal.1995 because of its higher incidence of disease; 108:1150-5.).Traditional operation methods such as coronary bypass are difficult to be used widely because of the restriction that is subject to the donor shortage, and the organizational engineering method has represented important application prospect (Langer R, Vacanti J.Tissue engineering.Science.1993; 260:920-6.).At present, a large amount of natural materials and polymeric material are used for the standby scaffold for vascular tissue engineering of electro-spinning, and the tissue engineering bracket of the nanostructured that prepare by electrostatic spinning technique is tissue repair and the potential of regenerating and providing huge.the nano-scale fiber structure of electrostatic spinning technique preparation is similar to the physical arrangement of protein fibre in the n cell epimatrix, can imitate to greatest extent human body n cell epimatrix, and be the adhesion of cell, propagation provides space (Mun CH more widely with regeneration, Jung Y, Kim SH, Lee SH, Kim HC, Kwon IK.Three-dimensional electrospun poly (lactide-co-varepsilon-caprolactone) for small-diameter vascular grafts.Tissue engineering PartA.2012, 18:1608-16.).
Yet the character of natural blood vessel requires the scaffold for vascular tissue engineering of preparation not only to have good biocompatibility and patency rate, also require to have certain stability and mechanics support, and small-caliber vascular tissue repair and regeneration are to higher (the Zheng W of this requirement, Wang Z, Song L, Zhao Q, Zhang J, Li D, et al.Endothelialization and patency of RGD-functionalized vascular grafts in a rabbit carotid artery model.Biomaterials.2012; 33:2880-91.).Up to the present there is not yet report the method that collagen, shitosan and P (LLA-CL) composite nano fiber electrostatic spinning technique is applied to the small-caliber vascular organizational project is arranged.collagen is a kind of native protein, shitosan is a kind of natural polysaccharide, preparing composite nano fiber by electrostatic spinning technique can be from forming and structure simulation n cell epimatrix, the material P (LLA-CL) of the similar blood vessel elasticity of blend simultaneously is to provide mechanical property preferably, like this natural material and synthetic material cospinning are in the same place, can overcome the deficiency of natural biological Polymer Mechanical performance, can avoid again synthetic material in the defective of biocompatibility and security, will have wide practical use in cardiovascular organization reparation and regeneration small-caliber vascular Tissue Engineering Study.
Summary of the invention
technical problem to be solved by this invention is to provide the preparation method of a kind of albumen-polysaccharide-polylactic acid poly caprolactone intravascular stent, the present invention will be similar to native protein-collagen and the natural polysaccharide-shitosan and the P(LLA-CL with good mechanical property of human body n cell epimatrix first) blend, prepare three component composite nano fiber tubular brackets by electrostatic spinning technique, the set of this kind support natural material and polymeric material advantage, make mechanical property and the biocompatibility of support reach optimum balance, and promote reparation and the regeneration of wounded tissue along with degradation in vivo.
The preparation method of a kind of albumen-polysaccharide of the present invention-polylactic acid poly caprolactone intravascular stent comprises:
(1) shitosan is dissolved in the mixed solution of hexafluoroisopropanol and trifluoroacetic acid, dissolving obtains chitosan solution fully;
(2) collagen is dissolved in hexafluoroisopropanol, dissolving obtains collagen solution fully;
(3) the polylactic acid poly caprolactone is dissolved in hexafluoroisopropanol, dissolving obtains polylactic acid poly caprolactone solution fully;
(4) with above-mentioned shitosan, collagen and polylactic acid poly caprolactone solution mix, stir, obtain albumen-polysaccharide-polylactic acid poly caprolactone spinning solution, then carry out electrostatic spinning, namely get albumen-polysaccharide-polylactic acid poly caprolactone intravascular stent, shitosan wherein, the volume ratio of collagen and polylactic acid poly caprolactone solution is 20～60:5～15:25～75, shitosan, the quality percent by volume of collagen and polylactic acid poly caprolactone solution is 8%, so the quality percent by volume that the rear total soluble matters of even mixing accounts for solvent is that the 8%(solute is shitosan, collagen and polylactic acid poly caprolactone).
In described step (1), the volume ratio of hexafluoroisopropanol and trifluoroacetic acid is 9:1.
In described step (1), the mass volume ratio concentration of chitosan solution is 8%.
In described step (2), the mass volume ratio concentration of collagen solution is 8%.
In described step (3), the mass volume ratio concentration of polylactic acid poly caprolactone solution is 8%.
In described step (4), the technological parameter of electrostatic spinning is: voltage 14KV, injection speed 1.0ml/h, receiving range are 15-18cm, adopt roller as receiving system.
In described step (4), the volume ratio of shitosan, collagen and polylactic acid poly caprolactone solution is 20:5:75,40:10:50 or 60:15:25.
Collagen, shitosan and P(LLA-CL in described step (4)) volume ratio be 20:5:75, collagen, shitosan and P(LLA-CL) mass ratio be 20:5:75.
Collagen, shitosan and P(LLA-CL in described step (4)) volume ratio be 40:10:50, collagen, shitosan and P(LLA-CL) mass ratio be 40:10:50.
Collagen, shitosan and P(LLA-CL in described step (4)) volume ratio be 60:15:25, collagen, shitosan and P(LLA-CL) mass ratio be 60:15:25.
Beneficial effect
(1) the present invention will be similar to native protein-collagen and the natural polysaccharide-shitosan and the P(LLA-CL with good mechanical property of human body n cell epimatrix first) blend, prepare three component composite nano fiber tubular brackets by electrostatic spinning technique, the set of this kind support natural material and polymeric material advantage, make mechanical property and the biocompatibility of support reach optimum balance, and promote reparation and the regeneration of wounded tissue along with degradation in vivo.
(2) the multicomponent composite biomaterial of the present invention's design is with a wide range of applications, and the preparation method is simple simultaneously, will have important application in the small-caliber vascular organizational project.
Description of drawings
Fig. 1 electrospinning process prepares the schematic diagram of three component intravascular stents;
Fig. 2 gross mass volume ratio is 8%, and wherein collagen-chitin-P (LLA-CL) mass ratio is the Combined Electrostatic spinning nano fibre stereoscan photograph of 20:5:75;
Fig. 3 gross mass volume ratio is 8%, and wherein collagen-chitin-P (LLA-CL) mass ratio is the Combined Electrostatic spinning nano fibre stereoscan photograph of 40:10:50;
Fig. 4 gross mass volume ratio is 8%, and wherein collagen-chitin-P (LLA-CL) mass ratio is the Combined Electrostatic spinning nano fibre stereoscan photograph of 60:15:25;
Fig. 5 gross mass volume ratio is 8%, and wherein collagen-chitin-P (LLA-CL) mass ratio is the photo of the Combined Electrostatic spinning nano fibre pipe of 20:5:75.
The specific embodiment
Below in conjunction with specific embodiment, further set forth the present invention.Should be understood that these embodiment only to be used for explanation the present invention and be not used in and limit the scope of the invention.Should be understood that in addition those skilled in the art can make various changes or modifications the present invention after the content of having read the present invention's instruction, these equivalent form of values fall within the application's appended claims limited range equally.
Take respectively with electronic balance collagen, shitosan and the P (LLA-CL) that quality is 0.8g; The collagen of 0.8g is dissolved in the 10ml hexafluoroisopropanol, and magnetic agitation is to dissolving fully; The shitosan of 0.8g is dissolved in 10ml hexafluoroisopropanol/trifluoroacetic acid (V/V, 9/1) mixed solvent, and magnetic agitation is to dissolving fully; The P (LLA-CL) of 0.8g is dissolved in the 10ml hexafluoroisopropanol, and magnetic agitation is to dissolving fully; After three kinds of solution dissolve fully, get the 20:5:75 mixing by volume of 2ml collagen solution, 0.5ml chitosan solution, 7.5ml P (LLA-CL) solution, magnetic agitation mixes and obtains total concentration is 8% blend spinning liquid 10ml, and its solute collagen-chitin-P (LLA-CL) mass ratio is 20:5:75.Be 1ml/h with controlling the micro-injection pump fltting speed in the mixed solution inhalation syringe, select No. 7 stainless steel syringe needles to be connected with the 14KV high pressure phase, the rotating speed of sentencing 800rpm at distance syringe needle 18cm with the roller that is covered with aluminium foil of ground connection can receive random nanofiber and obtain the nanofiber pipe.
Take respectively with electronic balance collagen, shitosan and the P (LLA-CL) that quality is 0.8g; The collagen of 0.8g is dissolved in the 10ml hexafluoroisopropanol, and magnetic agitation is to dissolving fully; The shitosan of 0.8g is dissolved in 10ml hexafluoroisopropanol/trifluoroacetic acid (V/V, 9/1) mixed solvent, and magnetic agitation is to dissolving fully; The P (LLA-CL) of 0.8g is dissolved in the 10ml hexafluoroisopropanol, and magnetic agitation is to dissolving fully; After three kinds of solution dissolve fully, get the 40:10:50 mixing by volume of 4ml collagen solution, 1ml chitosan solution, 5ml P (LLA-CL) solution, magnetic agitation mixes and obtains total concentration is 8% blend spinning liquid 10ml, and its solute collagen-chitin-P (LLA-CL) mass ratio is 40:10:50.Be 1ml/h with controlling the micro-injection pump fltting speed in the mixed solution inhalation syringe, select No. 7 stainless steel syringe needles to be connected with the 14KV high pressure phase, the rotating speed of sentencing 800rpm at distance syringe needle 15cm with the roller that is covered with aluminium foil of ground connection can receive random nanofiber and obtain the nanofiber pipe.
Take respectively with electronic balance collagen, shitosan and the P (LLA-CL) that quality is 0.8g; The collagen of 0.8g is dissolved in the 10ml hexafluoroisopropanol, and magnetic agitation is to dissolving fully; The shitosan of 0.8g is dissolved in 10ml hexafluoroisopropanol/trifluoroacetic acid (V/V, 9/1) mixed solvent, and magnetic agitation is to dissolving fully; The P (LLA-CL) of 0.8g is dissolved in the 10ml hexafluoroisopropanol, and magnetic agitation is to dissolving fully; After three kinds of solution dissolve fully, get the 60:15:25 mixing by volume of 6ml collagen solution, 1.5ml chitosan solution, 2.5ml P (LLA-CL) solution, magnetic agitation mixes and obtains total concentration is 8% blend spinning liquid 10ml, and its solute collagen-chitin-P (LLA-CL) mass ratio is 60:15:25.Be 1ml/h with controlling the micro-injection pump fltting speed in the mixed solution inhalation syringe, select No. 7 stainless steel syringe needles to be connected with the 14KV high pressure phase, can receive random nanofiber with the roller that is covered with aluminium foil of ground connection at the rotating speed that distance syringe needle 15cm sentences 800rpm, obtain internal diameter 3mm, the nanofiber pipe of length 5mm.
Claims (7)
1. the preparation method of albumen-polysaccharide-polylactic acid poly caprolactone intravascular stent comprises:
(1) shitosan is dissolved in the mixed solution of hexafluoroisopropanol and trifluoroacetic acid, dissolving obtains chitosan solution fully;
(2) collagen is dissolved in hexafluoroisopropanol, dissolving obtains collagen solution fully;
(3) the polylactic acid poly caprolactone is dissolved in hexafluoroisopropanol, dissolving obtains polylactic acid poly caprolactone solution fully;
(4) above-mentioned shitosan, collagen and polylactic acid poly caprolactone solution are mixed, stir, obtain albumen-polysaccharide-polylactic acid poly caprolactone spinning solution, then carry out electrostatic spinning, namely get albumen-polysaccharide-polylactic acid poly caprolactone intravascular stent, wherein the volume ratio of shitosan, collagen and polylactic acid poly caprolactone solution is 20～60:5～15:25～75, and the quality percent by volume that total soluble matters accounts for solvent is 8%.
2. the preparation method of a kind of albumen-polysaccharide according to claim 1-polylactic acid poly caprolactone intravascular stent is characterized in that: in described step (1), the volume ratio of hexafluoroisopropanol and trifluoroacetic acid is 9:1.
3. the preparation method of a kind of albumen-polysaccharide according to claim 1-polylactic acid poly caprolactone intravascular stent is characterized in that: in described step (1), the mass volume ratio concentration of chitosan solution is 8%.
4. the preparation method of a kind of albumen-polysaccharide according to claim 1-polylactic acid poly caprolactone intravascular stent is characterized in that: in described step (2), the mass volume ratio concentration of collagen solution is 8%.
5. the preparation method of a kind of albumen-polysaccharide according to claim 1-polylactic acid poly caprolactone intravascular stent is characterized in that: in described step (3), the mass volume ratio concentration of polylactic acid poly caprolactone solution is 8%.
6. the preparation method of a kind of albumen-polysaccharide according to claim 1-polylactic acid poly caprolactone intravascular stent, it is characterized in that: in described step (4), the technological parameter of electrostatic spinning is: voltage 14KV, injection speed 1.0ml/h, receiving range is 15-18cm, adopts roller as receiving system.
7. the preparation method of a kind of albumen-polysaccharide according to claim 1-polylactic acid poly caprolactone intravascular stent is characterized in that: in described step (4), the volume ratio of shitosan, collagen and polylactic acid poly caprolactone solution is 20:5:75,40:10:50 or 60:15:25.
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Cited By (11)
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| CN104005179A (en) * | 2014-06-13 | 2014-08-27 | 东华大学 | Method for preparing polycaprolactone-keratin composite nanometer fiber pipe |
| EP3015120A4 (en) * | 2013-06-28 | 2016-06-29 | Medprin Regenerative Medical Technologies Co Ltd | Tissue repair scaffold and preparation method and purpose thereof |
| CN107281558A (en) * | 2017-05-31 | 2017-10-24 | 苏州蔻美新材料有限公司 | A kind of preparation method of degradable blood vessel support |
| CN107296979A (en) * | 2017-07-02 | 2017-10-27 | 东华大学 | A kind of organizational project nanofiber intravascular stent and preparation method thereof |
| CN107296982A (en) * | 2017-05-31 | 2017-10-27 | 苏州蔻美新材料有限公司 | A kind of preparation method of fiber artificial's blood vessel |
| CN107899086A (en) * | 2017-11-06 | 2018-04-13 | 山东大学 | A kind of collagen nanofiber vascular repair material of hyaluronic acid oligosaccharide modification and preparation method thereof |
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Cited By (12)
| Publication number | Priority date | Publication date | Assignee | Title |
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| EP3015120A4 (en) * | 2013-06-28 | 2016-06-29 | Medprin Regenerative Medical Technologies Co Ltd | Tissue repair scaffold and preparation method and purpose thereof |
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| CN107296979A (en) * | 2017-07-02 | 2017-10-27 | 东华大学 | A kind of organizational project nanofiber intravascular stent and preparation method thereof |
| CN107899086A (en) * | 2017-11-06 | 2018-04-13 | 山东大学 | A kind of collagen nanofiber vascular repair material of hyaluronic acid oligosaccharide modification and preparation method thereof |
| CN107929817A (en) * | 2017-12-01 | 2018-04-20 | 蒋文明 | A kind of preparation method of degradable blood vessel bracket material |
| CN111821515A (en) * | 2020-08-10 | 2020-10-27 | 青海创铭医疗器械有限公司 | Chitosan-human-derived recombinant collagen electrostatic spinning nanofiber scaffold and preparation method thereof |
| CN112704768A (en) * | 2020-11-30 | 2021-04-27 | 山东大学 | Chondroitin sulfate modified collagen/polycaprolactone vascular repair stent and preparation method and application thereof |
| CN116212111A (en) * | 2023-03-16 | 2023-06-06 | 青岛大学附属医院 | Gelatin polycaprolactone protein peptide composite aerogel for cartilage repair and preparation method thereof |
| CN116212111B (en) * | 2023-03-16 | 2023-12-22 | 青岛大学附属医院 | Gelatin polycaprolactone protein peptide composite aerogel for cartilage repair and preparation method thereof |
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Application publication date: 20130612 |